Markers of and risk factors for the development and progression of diabetic kidney disease

Richard MacIsaac, Elif Ekinci, George Jerums

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Diabetic kidney disease (DKD) occurs in 25%-40% of patients with diabetes. Given the dual problems of a significant risk of progression from DKD to end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality, it is important to identify patients at risk of DKD and ESRD and initiate protective renal and cardiovascular therapies. The importance of preventive therapy is emphasized further by worldwide increases in the incidence of diabetes. This review summarizes the evidence regarding the prognostic value and benefits of targeting established and novel risk markers for DKD development and progression. Family history of DKD, smoking history, and glycemic, blood pressure, and plasma lipid level control are established factors for identifying people at greatest risk of DKD development and progression. Absolute albumin excretion rate (AER) and glomerular filtration rate (GFR) measurements also are important, although AER categorization generally lacks the necessary specificity and sensitivity, and estimates of declining GFR are compromised by methodological limitations for GFRs in the normal-to-high range. Emerging risk markers for progressive loss of kidney function include markers of oxidation and inflammation, profibrotic cytokines, uric acid, advanced glycation end products, functional and structural markers of vascular dysfunction, kidney structural changes, and tubular biomarkers. Among these, the most promising are serum uric acid and soluble tumor necrosis factor receptor (type 1 and type 2) levels, especially in relation to GFR changes. At present, these can only be considered as risk markers because they only identify an individual at increased risk of progressive DKD and not necessarily related to the causal pathway promoting kidney damage. Further work is needed to establish whether modulating these factors improves the prognosis in DKD. Although change in urinary peptidome levels also is a promising marker, there currently is neither a clinical assay nor adequate studies defining its prognostic value. Until these or other novel markers become available for clinical use, predictive accuracy often may be increased with greater attention to established markers. � 2014 by the National Kidney Foundation, Inc.
    Original languageEnglish
    Pages (from-to)S39-S62
    Number of pages24
    JournalAmerican Journal of Kidney Diseases
    Volume63
    Issue number2, Supplement 2
    DOIs
    Publication statusPublished - 2014

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    Diabetic Nephropathies
    Kidney
    Glomerular Filtration Rate
    Uric Acid
    Chronic Kidney Failure
    Disease Progression
    Albumins
    Receptors, Tumor Necrosis Factor, Type II
    Receptors, Tumor Necrosis Factor, Type I
    Advanced Glycosylation End Products
    Blood Vessels
    Biomarkers
    Smoking
    History
    Cytokines
    Blood Pressure
    Inflammation
    Morbidity
    Lipids
    Sensitivity and Specificity

    Cite this

    MacIsaac, Richard ; Ekinci, Elif ; Jerums, George. / Markers of and risk factors for the development and progression of diabetic kidney disease. In: American Journal of Kidney Diseases. 2014 ; Vol. 63, No. 2, Supplement 2. pp. S39-S62.
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    Markers of and risk factors for the development and progression of diabetic kidney disease. / MacIsaac, Richard; Ekinci, Elif; Jerums, George.

    In: American Journal of Kidney Diseases, Vol. 63, No. 2, Supplement 2, 2014, p. S39-S62.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Markers of and risk factors for the development and progression of diabetic kidney disease

    AU - MacIsaac, Richard

    AU - Ekinci, Elif

    AU - Jerums, George

    PY - 2014

    Y1 - 2014

    N2 - Diabetic kidney disease (DKD) occurs in 25%-40% of patients with diabetes. Given the dual problems of a significant risk of progression from DKD to end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality, it is important to identify patients at risk of DKD and ESRD and initiate protective renal and cardiovascular therapies. The importance of preventive therapy is emphasized further by worldwide increases in the incidence of diabetes. This review summarizes the evidence regarding the prognostic value and benefits of targeting established and novel risk markers for DKD development and progression. Family history of DKD, smoking history, and glycemic, blood pressure, and plasma lipid level control are established factors for identifying people at greatest risk of DKD development and progression. Absolute albumin excretion rate (AER) and glomerular filtration rate (GFR) measurements also are important, although AER categorization generally lacks the necessary specificity and sensitivity, and estimates of declining GFR are compromised by methodological limitations for GFRs in the normal-to-high range. Emerging risk markers for progressive loss of kidney function include markers of oxidation and inflammation, profibrotic cytokines, uric acid, advanced glycation end products, functional and structural markers of vascular dysfunction, kidney structural changes, and tubular biomarkers. Among these, the most promising are serum uric acid and soluble tumor necrosis factor receptor (type 1 and type 2) levels, especially in relation to GFR changes. At present, these can only be considered as risk markers because they only identify an individual at increased risk of progressive DKD and not necessarily related to the causal pathway promoting kidney damage. Further work is needed to establish whether modulating these factors improves the prognosis in DKD. Although change in urinary peptidome levels also is a promising marker, there currently is neither a clinical assay nor adequate studies defining its prognostic value. Until these or other novel markers become available for clinical use, predictive accuracy often may be increased with greater attention to established markers. � 2014 by the National Kidney Foundation, Inc.

    AB - Diabetic kidney disease (DKD) occurs in 25%-40% of patients with diabetes. Given the dual problems of a significant risk of progression from DKD to end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality, it is important to identify patients at risk of DKD and ESRD and initiate protective renal and cardiovascular therapies. The importance of preventive therapy is emphasized further by worldwide increases in the incidence of diabetes. This review summarizes the evidence regarding the prognostic value and benefits of targeting established and novel risk markers for DKD development and progression. Family history of DKD, smoking history, and glycemic, blood pressure, and plasma lipid level control are established factors for identifying people at greatest risk of DKD development and progression. Absolute albumin excretion rate (AER) and glomerular filtration rate (GFR) measurements also are important, although AER categorization generally lacks the necessary specificity and sensitivity, and estimates of declining GFR are compromised by methodological limitations for GFRs in the normal-to-high range. Emerging risk markers for progressive loss of kidney function include markers of oxidation and inflammation, profibrotic cytokines, uric acid, advanced glycation end products, functional and structural markers of vascular dysfunction, kidney structural changes, and tubular biomarkers. Among these, the most promising are serum uric acid and soluble tumor necrosis factor receptor (type 1 and type 2) levels, especially in relation to GFR changes. At present, these can only be considered as risk markers because they only identify an individual at increased risk of progressive DKD and not necessarily related to the causal pathway promoting kidney damage. Further work is needed to establish whether modulating these factors improves the prognosis in DKD. Although change in urinary peptidome levels also is a promising marker, there currently is neither a clinical assay nor adequate studies defining its prognostic value. Until these or other novel markers become available for clinical use, predictive accuracy often may be increased with greater attention to established markers. � 2014 by the National Kidney Foundation, Inc.

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    KW - connective tissue growth factor

    KW - cystatin C

    KW - fatty acid binding protein

    KW - fibroblast growth factor 23

    KW - kidney injury molecule 1

    KW - lipid

    KW - matrix protein

    KW - neutrophil gelatinase associated lipocalin

    KW - transforming growth factor beta

    KW - tumor necrosis factor receptor 1

    KW - tumor necrosis factor receptor 2

    KW - uric acid

    KW - albuminuria

    KW - article

    KW - blood pressure

    KW - diabetic nephropathy

    KW - disease course

    KW - dyslipidemia

    KW - family history

    KW - genetic marker

    KW - glomerulus filtration rate

    KW - glycemic control

    KW - human

    KW - hyperglycemia

    KW - hypertension

    KW - inflammation

    KW - kidney function

    KW - kidney injury

    KW - kidney size

    KW - lipid blood level

    KW - microalbuminuria

    KW - oxidation

    KW - oxidative stress

    KW - pathophysiology

    KW - prognosis

    KW - protein glycosylation

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    KW - Diabetes mellitus

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    KW - Biological Markers

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    KW - Kidney

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    U2 - 10.1053/j.ajkd.2013.10.048

    DO - 10.1053/j.ajkd.2013.10.048

    M3 - Article

    VL - 63

    SP - S39-S62

    JO - American Journal of Kidney Diseases

    JF - American Journal of Kidney Diseases

    SN - 0272-6386

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    ER -